Age and strain differences in the activities of the neurotransmitter synthetic enzymes, choline acetyltransferase, glutamic acid decarboxylase and tyrosine hydroxylase were demonstrated in two strains of mice, A/J and C57BL/6J, between 4, 18 and 24 months. Age changes in neurochemical profiles therefore vary with genetic strain. Striatal slices from the rat brain are less able to release acetylcholine in response to apomorphine, if they are derived from senescent as compared to young mature rats. The reduced ability corresponds to reduced motor behavior in older rats. Binding of receptors for excitory amino acid neurotransmitters in the rat brain was evaluated in relation to treatment with the modulator, phenylalanyl-L-glutamate. This modulator increased the number of binding sites, to a greater extent in the striatum of brains of 34-month-old rats than of 3-month-old mature rats. Rats made diabetic by administration of streptozotocin showed decreased in the activity of tyrosine hydroxylase, and increased concentrations of norepinephrine, in various brain regions, including the thalamus and hypothalamus. These results suggest that diabetes can alter brain monoamine metabolism and behavior subserved by monoamine neurotransmitters.